B7H3 CAR-T therapy in relation to tumor growth in skin tumor.
Authors: Gang Hu, Yunsheng Liang, Guangchao Li, Wen Ding, min luo
Journal: Journal of Clinical Oncology (2022)

e21502 Background: Exciting progress has been recently witnessed on the development of chimeric antigen receipt T cell (CAR-T) therapy for hematopoietic malignancies. The biological principles of CAR-T therapy are applicable to solid tumors but very little success has been achieved due to various challenges intrinsic to solid tumors. The development of new solid tumor targets is particularly important. CD276 (B7H3) is one of the most promising therapeutic targets for solid tumors and has been extensively tested in preclinical trials. However, no clinical trials have been reported on its efficacy and safety. In this study, we report a case of relapsed basal cell carcinoma (BCC) patient treated with B7H3 CAR-T cells through direct intra-tumor injection. Trial registration number: ChiCTR2100044386. Methods: We have generated a 2 nd generation of B7H3 CAR-T, the extracellular scFv was derived from a humanized B7H3 monoclonal antibody, which was generated by hybridoma technology. Autologous CAR-T cells were manufactured in a cGMP facility. CAR-T cells were given by three dose-escalated intra-tumor injections without lymphodepletion conditioning. Results: A 65-year-old man was initially diagnosed with multiple BCC, the disease relapsed and spread to all over the body. Immunohistochemical staining of the tumor tissue showed positive for B7H3 (80%, ++̃+++). The patient received autologous anti-B7H3 CAR-T therapy cells through intra-tumor injection three times with dose escalation on day 1, day 14 and day 62. There were two different tumor sites that were treated in this patient (site 1 for abdominal tumor 1.8 cm × 0.6 cm; site 2 for forehead tumor 6 cm × 6 cm). For the adverse events, the patient’s AST/ALT levels slightly increased about two fold after the first infusion. However, we did not observe increases of AST/ALT levels after the second and third infusion, even with much higher dose. After three infusions, the volume of original lesion in the abdomen decreased 40% (1.8cm × 0.6cm to 1.3cm × 0.5cm), shrinking from bulging to flat. The large lesion in the forehead became dry from original ulcer and bleeding. We further performed surgery to remove the remained tumor in the abdomen after the third infusion. IHC analysis demonstrated that the percentage of B7H3 positive cells decreased from 80% to about 40%, and the intensity also decreased from ++̃+++ to +. Meanwhile, CD3 T cells increased in the tumor site, but failed to efficiently infiltrate into neighboring tumor areas, which was marked by high level of TGF-β. Conclusions: In this case, we reported for the first time that a patient with skin tumor achieved a partial response after receiving repeated intra-tumor injections of anti-B7H3 CAR-T cells. This study demonstrated that B7-H3 CAR-T cell therapy is a safe and promising treatment for relapsed skin tumor. Combination with other strategies to improve CAR-T cell infiltration in the tumor site may help to further improve the clinical response. Clinical trial information: ChiCTR2100044386.